1. Field of the Invention
The invention relates to the preparation of novel cyclisation substrates for steroidal compounds, and also relates to the conversion of these cyclisation substrates into novel steroidal compounds, in particular, 7.alpha.-substituted steroids of the oestrane series.
2. Prior Art and Other Information
The stereospecific cyclisation of a compound of formula I: ##STR3## into a compound of formula II: ##STR4## is described in 98 J.A.C.S. 1038 (1976).
Only the equatorial 11.alpha.-methyl derivative is formed. The cyclisation of a (pro)-11-hydroxy compound also results exclusively in the 11.alpha.-hydroxy steroid (98 J.A.C.S. 1039 (1976)).
When this cyclisation is performed in the (pro)-19-nor-series (R is H), it proves that no stereo-selectivity occurs (see T. M. Yarnell, Dissertation, Stanford University, July 1975, in 1976 DISSERTATION ABSTRACTS INTERN, 1976, B36 no. 10, page 5054). A mixture of 11.alpha.- and 11.beta.-substituted steroids in molar proportions of about 1:1 is formed.
Related compounds by structure to those of formulae III-V of the instant invention and processes for converting 1-aryl-8,11-bis(ethylenedioxy)-3-dodecene compounds to 3-alkyl-2-[(E)-6'-(aryl)-3'-hexenyl]-2-cyclopentenones and subsequently via cyclopentenols to 17-substituted-.DELTA..sup.1,3,5(10),13(17) -gonatetraenes are disclosed in British Pat. No. 1 448 873 and 95 J.A.C.S. 7501-7504 (1973).
The present invention provides a method of producing 7.alpha.-substituted analogues of the steroidal compounds disclosed in British Pat. No. 1 448 873 (such as 7.alpha.-methyl-oestrone by cyclizing 2-[(E)-6-aryl-3-hexenyl]-cyclopentenols of which the hexenyl group has been substituted in position 5. Steroids which may be prepared according to the method of the present invention are disclosed inter alia in U.S. Pat. No. 3,627,894 (7.alpha.-methyl-estrones), U.S. Pat. No. 3,574,197 (1-hydroxy-7.alpha.-methyl-estrane derivatives), U.S. Pat. No. 3,944,576 (7.alpha.-methoxymethyl-estrane derivatives) and U.S. Pat. Nos. 3,318,925/26/27/28/29 (7.alpha.-methyl-.DELTA..sup.1,3,5(10) -estratriene derivatives).